Diisopropylcarbodiimide → HCID 59286587, compound

HRID 1876034Notes

Reaction equation

HRID 1876034 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[CH:8]=[N:7][C:6]([NH:14][C:15]([NH:17][CH2:18][C@@:19]1([OH:27])[CH:24]3[CH2:25][CH2:26][N:21]([CH2:22][CH2:23]3)[CH2:20]1)=S)=[CH:5]2.C(=NC(C)C)=NC(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[CH:8]=[N:7][C:6]([NH:14][C:15]1[O:27][C@:19]3([CH2:18][N:17]=1)[CH:24]1[CH2:25][CH2:26][N:21]([CH2:22][CH2:23]1)[CH2:20]3)=[CH:5]2

Participants

4

Reactant 2

HCID 12734DiisopropylcarbodiimideHCID 59286546HCID 59286546, compound

Product 1

HCID 59286587HCID 59286587, compoundYield 24.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of (S)-1-(6-chloro-7-methoxyisoquinolin-3-yl)-3-((3-hydroxyquinuclidin-3-yl)methyl)thiourea (140 mg, 0.344 mmol) in DMF (2.5 mL) was added a solution of N,N′-methanediylidenedipropan-2-amine (101 mg, 0.800 mmol) in DMF (0.5 mL) and the resulting mixture was allowed to stand at room temperature for 10 days. The solvent was then evaporated in vacuo. The residue was dissolved in ˜5 mL MeOH (some white solid was filtered off, 09) and subjected to preparative HPLC purification followed by silica gel chromatography in 1% NH4OH/9% MeOH/90% CHCl3 to give 31 mg (24%) (R)—N-(6-chloro-7-methoxyisoquinolin-3-yl)-4H-1′-azaspiro[oxazole-5,3′-bicyclo[2.2.2]octan]-2-amine LCMS RT 1.04 min, MH+=373.2, 375.2 1H NMR (500 MHz, MeOD) δ ppm 8.78-8.89 (1H, m), 7.90-8.01 (1H, m), 7.14-7.23 (1H, m), 4.01 (3H, s), 3.95-3.99 (1H, m), 3.62-3.71 (1H, m), 3.19-3.25 (1H, m), 3.06-3.13 (1H, m), 2.90-3.00 (2H, m), 2.76-2.89 (2H, m), 2.10-2.21 (2H, m), 1.69-1.83 (2H, m), 1.56-1.68 (1H, m).

Workup

  1. customThe solvent was then evaporated in vacuo
  2. dissolutionThe residue was dissolved in ˜5 mL MeOH (some white solid
  3. filtrationwas filtered off
  4. custom09) and subjected to preparative HPLC purification

Sources & evidence

ORD record
ord-39f3254a0bcf4e45b75bd8890265f162
Source dataset
uspto-grants-2012_11
Patent number
US08309577B2

Reaction notes

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